BRIDGE: An Open-Label Phase II Trial Evaluating the Safety of Bevacizumab plus Carboplatin/Paclitaxel as First-Line Treatment for Patients with Advanced, Previously Untreated, Squamous Non-small Cell Lung Cancer

Background: Patients with predominantly squamous non-small cell lung cancer (NSCLC) have been generally excluded from studies of bevacizumab treatment, because squamous histology was identified as a possible risk factor for severe (grade >= 3) pulmonary hemorrhage (PH) in a phase II study. BRIDGE was designed to determine whether delaying initiation of bevacizumab treatment and selecting patients without baseline risk factors for PH would lower the incidence of severe PH among patients with squamous NSCLC. Methods: Patients in this open-label, single-arm study were treated with carboplatin/paclitaxel for two cycles, followed by carboplatin/paclitaxel and bevacizumab in cycles 3 to 6, followed by bevacizumab until progression or unacceptable toxicity. Eligible patients had stage IIIb, stage IV, or recurrent squamous NSCLC. The primary end point was incidence of grade >= 3 PH. Results: Grade >= 3 PH occurred in 1 of 31 patients who received >= 1 dose of bevacizumab: estimated incidence was 3.2% (90% confidence interval 0.3-13.5%). The patient experienced grade 3 PH, discontinued from the study, then experienced grade 4 PH 10 days later, and died of progressive disease. No other serious bleeding events occurred. Nine patients (29.0%) experienced grade 3 adverse events, including five with hypertension; five patients experienced grade 4 adverse events (dyspnea, PH, basal ganglia infarction, cerebral ischemia, and pain). Median progression-free survival was 6.2 months (95% confidence interval 5.32-7.62 months). Conclusions: The incidence of grade >= 3 PH was 3.2% (one patient). No new safety signals were identified. Although the rate of PH was low, the number of patients in this study was also low. Treatment of squamous NSCLC with bevacizumab should be considered experimental.